Overactivation of AMPA receptor but not NMDA receptor contributes to motor deficits and motor neuron loss in GLAST+/−/GLT1-cKO mice. A, Perampanel treatment delayed motor deficits in the hanging wire test (n = 15 for vehicle-treated and n = 17 for perampanel-treated GLAST+/−/GLT1-cKO mice). *p < 0.05 (post hoc unpaired two-tailed t test at corresponding time point after two-way repeated-measures ANOVA). B, Amelioration of hindlimb paralysis in GLAST+/−/GLT1-cKO mice after perampanel treatment. Arrow indicates the fully paralyzed hindlimb of vehicle-treated GLAST+/−/GLT1-cKO mice. Arrowhead indicates the hindlimb upon which the perampanel-treated GLAST+/−/GLT1-cKO mice could stand. C, ChAT immunofluorescence of the lumbar ventral horn from control, vehicle-treated, and perampanel-treated GLAST+/−/GLT1-cKO mice at 7 weeks of age. Scale bar, 100 μm. D, Quantification of ChAT-positive motor neurons at 7 weeks of age (n = 3 for control mice, n = 4 for vehicle-treated mice, and n = 5 for perampanel-treated GLAST+/−/GLT1-cKO mice). *p < 0.05, ***p < 0.001 (post hoc Tukey HSD test after one-way ANOVA). E, Memantine treatment could not ameliorate motor deficits in the hanging wire test (n = 9 for vehicle-treated and n = 7 for memantine-treated GLAST+/−/GLT1-cKO mice). n.s., Not significant (two-way repeated-measures ANOVA). F, ChAT immunofluorescence of the lumbar ventral horn from vehicle-treated and memantine-treated GLAST+/−/GLT1-cKO mice at 7 weeks of age. Scale bar, 100 μm. G, Quantification of ChAT-positive motor neurons at 7 weeks of age (n = 3 for vehicle-treated and 4 for memantine-treated GLAST+/−/GLT1-cKO mice). n.s., Not significant (unpaired two-tailed t test). H, MK-801 treatment could not ameliorate motor deficits in the hanging wire test (n = 5 for vehicle-treated and 6 for MK-801-treated GLAST+/−/GLT1-cKO mice). n.s., Not significant (two-way repeated-measures ANOVA). I ChAT immunofluorescence of the lumbar ventral horn from vehicle-treated and MK-801-treated GLAST+/−/GLT1-cKO mice at 8 weeks of age. Scale bar, 100 μm. J, Quantification of ChAT-positive motor neurons at 8 weeks of age (n = 3 for each groups). n.s., Not significant (unpaired two-tailed t test). All data are expressed as the mean ± SEM.